A Phase III Randomised Study to Evaluate Dato DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor low/HER2-negative Breast Cancer
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
- Registration Number
- CTRI/2024/04/065322
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Inclusion criteria
Informed consent
Age
1.Participant must be 18 years, at the time of signing the ICF.
Type of Participant and Disease Characteristics
1.Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer defined as the following combined primary tumour T and regional lymph node N staging per AJCC for breast cancer staging system edition 8 as assessed by the investigator based on radiological and/or clinical assessment.
1.Negative for ER with 1 of tumour cells positive for ER on IHC and negative for PR with of tumour cells positive for PR on IHC, or hormone receptor-low and
TNBC or hormone receptor-low/HER2-negative breast cancer is defined as:
1.Negative for HER2 with 0 or 1 intensity on IHC, or 2 intensity on IHC and no evidence of amplification on ISH.
2.ECOG PS of 0 or 1.
3.Provision of acceptable tumour sample prior to randomisation as defined in the Laboratory Manual.
Note: Sample collected in China will comply with local regulatory approval.
1.Adequate bone marrow reserve and organ function within 7 days before randomisation, Sex and Contraceptive/Barrier Requirements
2.Male and/or female
Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Informed Consent
1.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
2.Provision of signed and dated written optional genetic research information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.
Other Inclusion Criteria
1.All races, gender and ethnic groups are eligible for this study.
Exclusion criteria
Medical conditions
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.As judged by the investigator, any evidence of diseases such as severe or uncontrolled systemic diseases, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
2.Refractory nausea and vomiting, inability to swallow a formulated product, or previous significant bowel resection, that would preclude adequate absorption, distribution, metabolism, or excretion of capecitabine or olaparib.
3.History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence.
4.Active or prior documented autoimmune or inflammatory disorders
5.Evidence of distant disease.
6.Clinically significant corneal disease.
7.Has active or uncontrolled hepatitis B or C virus infection.
7a. Are HBsAg-positive with chronic HBV infection
1.Known HIV infection that is not well controlled.
2.Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections.
3.Known to have active tuberculosis infection
4.Resting ECG with clinically significant abnormal findings.
5.Uncontrolled or significant cardiac disease
6.History of non-infectious ILD pneumonitis including radiation pneumonitis that required steroids, has current ILD pneumonitis, or has suspected ILD pneumonitis that cannot be ruled out by imaging at screening.
7.Has severe pulmonary function compromise.
Prior/Concomitant Therapy
1.Any concomitant medication known to be associated with torsades de pointes.
2.Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer.
3.Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of 14 days before randomisation.
4.Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention.
5.Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by central assessment of pCR. <br/ ><br> <br/ ><br>Timepoint: To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by central assessment of pCR. <br/ ><br> <br/ ><br>Baseline and 6 Months ( Post surgery) and 18 Months (Completion of adjuvant treatment) <br/ ><br>
- Secondary Outcome Measures
Name Time Method